Prehospital anesthesia in postcardiac arrest patients: a multicenter retrospective cohort study

Background Currently, the data regarding the impact of prehospital postcardiac arrest anesthesia on target hemodynamic and ventilatory parameters of early postresuscitation care and recommendations on its implementation are rare. The present study examines the incidence and impact of prehospital postcardiac arrest anesthesia on hemodynamic and ventilatory target parameters of postresuscitation care. Methods In this multicentre observational study between 2019 and 2021 unconscious adult patients after out-of-hospital-cardiac arrest with the presence of a return-of-spontaneous circulation until hospital admission were included. Primary endpoint was the application of postarrest anesthesia. Secondary endpoints included the medication group used, predisposing factors to its implementation, and its influence on achieving target parameters of postresuscitation care (systolic blood pressure: ≥ 100 mmHg, etCO2:35–45 mmHg, SpO2: 94–98%) at hospital handover. Results During the study period 2,335 out-of-hospital resuscitations out of 391,305 prehospital emergency operations (incidence: 0.58%; 95% CI 0.54–0.63) were observed with a return of spontaneous circulation to hospital admission in 706 patients (30.7%; 95% CI 28.8–32.6; female: 34.3%; age:68.3 ± 14.2 years). Postcardiac arrest anesthesia was performed in 482 patients (68.3%; 95% CI 64.7–71.7) with application of hypnotics in 93.4% (n = 451), analgesics in 53.7% (n = 259) and relaxants in 45.6% (n = 220). Factors influencing postcardiac arrest sedation were emergency care by an anesthetist (odds ratio: 2.10; 95% CI 1.34–3.30; P < 0.001) and treatment-free interval ≤ 5 min (odds ratio: 1.59; 95% CI 1.01–2.49; P = 0.04). Although there was no evidence of the impact of performing postcardiac arrest anesthesia on achieving a systolic blood pressure ≥ 100 mmHg at the end of operation (odds ratio: 1.14; 95% CI 0.78–1.68; P = 0.48), patients with postcardiac arrest anesthesia were significantly more likely to achieve the recommended ventilation (odds ratio: 1.59; 95% CI 1.06–2.40; P = 0.02) and oxygenation (odds ratio:1.56; 95% CI 1.04–2.35; P = 0.03) targets. Comparing the substance groups, the use of hypnotics significantly more often enabled the target values for etCO2 to be reached alone (odds ratio:2.79; 95% CI 1.04–7.50; P = 0.04) as well as in combination with a systolic blood pressure ≥ 100 mmHg (odds ratio:4.42; 95% CI 1.03–19.01; P = 0.04). Conclusions Postcardiac arrest anesthesia in out-of-hospital cardiac arrest is associated with early achievement of respiratory target parameters in prehospital postresuscitation care without evidence of more frequent hemodynamic complications. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-024-01864-x.

parameters of postresuscitation care in prehospital emergency medicine in Germany [4].

Methods
The study was approved by the Institutional Review Board of the University of Muenster on 03.10.2022,Germany file reference 2022-617-f-S).Procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration.Owing to its retrospective nature, the requirement of written informed consent was waived by the institutional review board.This article adheres to the applicable Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.
The study was based on the electronically recorded rescue service data across three prehospital emergency medical services (city of Dresden, districts of Gütersloh and Lippe, Germany) with a total of approximately 1,275,000 inhabitants in the Federal Republic of Germany between 01.01.2019 and 31.12.2021.There were no differences between these centers with regards to the emergency physician who intubated and the preference for a particular anesthetic agent.
In Germany, in life-threating emergencies like out-ofhospital-cardiac arrest, a paramedic ambulance and a medical intervention car, staffed by a paramedic and an emergency physician, are dispatched to the Scene of the emergency.
In Germany, emergency physicians complete a 40-h course to participate in prehospital emergency medicine after at least 1.5 years of training in a specialty such as anesthesia, intensive care medicine or emergency care.
The respective patient care reports of the resuscitations performed were evaluated, supplemented by data from the German Resuscitation Register.
Patients ≥ 18 years of age with prehospital resuscitation for out-of-hospital cardiac arrest of any cause (e.g.cardiac, hypoxic, etc. [see Table 1]), defined according to the Utstein criteria as the need for chest compressions and/or defibrillation, unconsciousness after prehospital return-of-spontaneous circulation, and spontaneous circulation at hospital admission were included [12].
Exclusion criteria were no out-of-hospital-cardiac arrest, no resuscitative measures performed, patient age < 18 years; no occurrence of return-of-spontaneous circulation; consciousness after occurrence of returnof-spontaneous circulation; patients in whom out-ofhospital-cardiac arrest occurred as a result of prehospital sedation and/or induction of anesthesia; death findings; do-not-resuscitate order; no hospital admission; no presence of sustained spontaneous circulation on hospital admission; and incomplete data.

Background
Out-of-hospital-cardiac arrest continues to be of extraordinary social relevance due to its high mortality and morbidity [1,2].In addition to strategies to shorten the treatment-free interval and to support early defibrillation, the importance of early, optimal postresuscitation care has received growing attention in recent years [3][4][5].
For prehospital emergency care in this context, early action according to the ABC concept; advanced airway management by means of intubation of the trachea performed by the most experienced provider available, in patients with persistent coma or other clinical indication for anesthesia; their capnographic control; sufficient ventilation with titration of FiO2 to achieve a reliably measured pulsoxymetric oxygen saturation (SpO2) between 94 and 98% while avoiding hyper-and hypoxemia and a target endtidal CO2 (etCO2) between 35 and 45 mmHg; the avoidance of hypotensive phases (target mean arterial pressure ≥ 65 mmHg respectively systolic blood pressure ≥ 100 mmHg) and targeted temperature management with temperatures between 32 and 36 °C is recommended [4,6].Based on these recommendations, both intubation of the trachea, if not already done during resuscitation, and optimal synchronization of the patient to the emergency respirator in this early phase of postresuscitation care, make postcardiac arrest anesthesia appear reasonable.In this context, various factors must be taken into account when weighing the pros and cons of postcardiac arrest anesthesia: Possible advantages are the reduction of oxygen consumption; facilitation of endotracheal intubation and improvement of tube tolerance as well as increased compliance with mechanical ventilation; induction of retrograde amnesia, analgesia and stress reduction; therapy of posthypoxic seizures; facilitated performance of interventions necessary immediately after hospital admission (e.g.coronary angiography); rapid induction of a possibly indicated target temperature management as well as potentially neuroprotective effects of various anesthetics [4,[7][8][9][10][11][13][14][15][16][17][18][19].Factors that count against postcardiac arrest anesthesia include hemodynamic side effects with possible rearrest, acute hypotension and subsequentially reduced cerebral perfusion; the risk of unnecessary induction of target temperature management with therapy-associated complications; delayed awakening in the intensive care unit with the prolongation of the duration of ventilation and intensive care stay and more difficult prognosis assessment [4,8,10,18].To date, little data and no well founded recommendations for performing prehospital postcardiac arrest anesthesia exist [8][9][10][11].The present multicenter observational study examines the frequency, performance, complications and impact of prehospital postcardiac arrest anesthesia on established target In addition to patient factors (age, sex, state of health before the onset of circulatory arrest, relevant comorbidities [cardiac, pulmonary, neurological, metabolic, malignant, immunodeficiency, not known]), the qualifications (doctor in training, specialist, not known) and specialization of the attending emergency physician (anesthesia, surgery, internal medicine, pediatrics, other, not known) were recorded.
In addition, data on circulatory arrest (suspected cause [cardiac, hypoxia, hemorrhage to death, trauma, sepsis, intracranial pathology, intoxication, metabolic, drowning, others, unknown]; duration of the treatmentfree interval, defined as time between collapse and start of chest compressions [≤ 5 min, 5-10 min, > 10 min, unknown]; initial heart rhythm [shockable vs. nonshockable]; number of defibrillations performed, initial airway management [extraglottic airway, intubation of the trachea, intubation of the trachea after returnof-spontaneous-circulation]; time of first epinephrine application and cumulative dose of epinephrine (mg); duration of resuscitation], complications in the course of the operation (airway complications, difficult airway management, defined as > 1 intubation attempt or need for procedure change, aspiration, re-arrest, hypotension), the antihypotensive therapy used following cardiac arrest (theodrenaline/cafedrine, norepinephrine, epinephrine), the use of postarrest anesthesia, and vital signs at hospital transfer (SpO2, etCO2, systolic blood pressure) and grouped according to the recommended target parameters of postarrest treatment (SpO 2 < 94%; 94-98%; > 98%; The postarrest hemodynamic and ventilatory management was set according to the judgment of the attending physician.The data on prehospital postcardiac arrest anesthesia included the substance used (analgesics such as opioids, hypnotics, neuromuscular blocking agents), dose and any combinations of different drugs used.
The primary endpoint was the use of anesthetics [hypnotics and/or analgesics and/or neuromuscular blocking agents] after out-of-hospital-cardiac arrest and returnof-spontaneous-circulation until hospital admission.Secondary endpoints included training level and specialty of attending emergency physicians; factors associated with cardiac arrest (presumed cause of cardiac arrest, duration of treatment-free interval, duration of resuscitation; resuscitation measures performed); complications in the course of the operation; and achievement of guideline target parameters for oxygenation, ventilation and blood pressure.

Statistical analysis
The data analysis and statistical plan was written and recorded in the investigators' files before data were accessed.We first performed a logistic regression to assess the association between specific covariates and allocation to postcardiac arrest anesthesia.As covariates we used the characteristics of the patients included, the emergency physicians involved and the resuscitation measures performed as shown in Table 1.In as second step we checked for potential association between allocation to postcardiac arrest anesthesia or nonpost cardiac arrest anesthesia and reaching the specific clinically relevant parameters of etCO2 within and without 35-45 mmHg, SpO2 within or without 94-98% and systolic blood pressure < 100 or ≥ 100 mmHg while adjusting for potential confounders using a logistic regression model.Odds ratio (OR) estimates are given with their 95% confidence intervals (95% CI) and p values.All analyses were performed using the statistical software SAS 9.4 (SAS Institute Inc, Cary, NC).

Results
In the study period between 01.01.2019 and 31.12.2021, a total of 2,335 out-of-hospital resuscitations out of 391,305 emergency cases were recorded in the participating study centers (incidence of out-of-hospital resuscitation: 0.59% of prehospital emergency operations per year; 95% CI 0.57-0.62;approximately 183.1 per 100,000 inhabitants and year; 95% CI 175.8-190.7).
Figure 1 shows an overview of the evaluated prehospital emergency operations after application of all inclusion and exclusion criteria.2298 reports were included, while 37 were excluded with incomplete datasets.
In 706 (30.7%; 95% CI 28.8-32.6) of these patients, a stable return-of-spontaneous circulation was achieved at hospital admission.Table 1 shows the patient's characteristics, the emergency physicians involved, the resuscitation measures performed, complications during the course of the operation and vital signs at the end of the operation.

Discussion
In this multicenter observational study prehospital postcardiac arrest anesthesia was performed in 68.3%.Factors associated with the performance of postcardiac arrest anesthesia were emergency medical care by an anesthesiologist or a treatment-free interval of ≤ 5 min.Patients who received postcardiac arrest anesthesia were significantly more likely to achieve the oxygenation and ventilation goals of postresuscitation care at hospital admission without evidence of an increased rate of hemodynamic complications.
Advanced airway management, as well as induction and maintenance of anesthesia represent highrisk procedures, especially in critically ill patients [8,10,13,14].To improve the quality and safety of care, recommendations for the management of intubation of the trachea and induction of anesthesia in critically ill and emergency patients have been developed [8,10,[15][16][17].In out-of-hospital cardiac arrest patients, intubation of the trachea is often performed during or soon after resuscitation.Induction of general anesthesia is sometimes useful for its implementation [4,6,15].Surprisingly, the postcardiac arrest patient population has not been considered in the current recommendations and it has so far been insufficiently evaluated, whether these recommendations are directly transferable to postcardiac arrest patients [4,8,10,16,17].The present study shows that prehospital postcardiac arrest anesthesia is frequently used and indicates the need to develop evidence-based recommendations and guidelines for its implementation.
The decision to initiate general anesthesia onsite is contingent upon several factors, including the feasibility Fig. 1 Flowchart of the applied inclusion and exclusion criteria.OHCA, out-of-hospital cardiac arrest; ROSC, return of spontaneous within the operational setting ("stay and play" versus "load and go").This entails considerations such as proximity to the nearest suitable hospital, available equipment (including potential spatial constraints within the emergency vehicle), the qualifications of the emergency medical personnel.In addition, the determination of whether to induce general anesthesia onsite is influenced by the confidence of the attending physician in administering such anesthesia.In this context, postcardiac arrest anesthesia was performed more frequently by anesthetists possibly due to their greater experience in anesthesia induction.The indications for anesthetic drugs could vary tremendously, and a binary definition may have influenced the biological significance of a dose-response relationship.However, based on the present findings, this would underline the importance of developing recommendations for postcardiac arrest anesthesia for nonanesthesiologists or for use in a nonphysician-based ambulance system.
The favorable influence of the shortest possible noflow or low-flow times on prognosis is known from studies [5,20,21].The higher likelihood of obtaining a postcardiac arrest anesthesia in the patient population with a treatment-free interval and therefore no-flow or low-flow times ≤ 5 min may indicate that these patients may possibly have shown signs of a more favorable outcome which made a postcardiac arrest anesthesia necessary (e.g.spontaneous respiration, return of protective reflexes) [21].In particular, this subpopulation could benefit most from performing a postcardiac arrest anesthesia: In the postresuscitation phase, patients are at risk of hypoxic-ischemic and hyperoxemic-reperfusion brain injury [4,[22][23][24].Control of paCO2 is important because of its importance for cerebral vascular tone besides avoidance of hypotensive phases and achievement of an adequate blood pressure, acting as determinant of cerebral perfusion [4].The available data indicates that the implementation of prehospital postcardiac arrest anesthesia is associated with a significant improvement in the achievement of ventilation and oxygenation goals of postresuscitation care without evidence of an increased  rate of hemodynamic complications or negative effects on the achievement of the recommended blood pressure goals.As part of a structured prehospital postresuscitation care, it could thus potentially be suitable to improve patient care in this particularly vulnerable phase, following the return-of-spontaneous circulation.So far, there are no recommendations regarding the optimum medication for postcardiac arrest anesthesia [4].The effects of different combinations of substances on intubation conditions and hemodynamics in critically ill patients have been investigated in numerous studies [8,10,16,17,25].Midazolam and propofol are potent vasodilators, carrying the risk of circulatory depression when administered in usual induction doses.However, these are widely used in the induction of anesthesia in critically ill patients, as also shown in the present study [10,11,26].The use of propofol is widespread in anesthesia, intensive care and emergency medicine, which may explain its frequent use in the present work.While the effects on hemodynamics during induction of anesthesia in critically ill patients are inconsistent in studies [10,11,16,27], experimental data in animal models show that propofol in the context of postresuscitation care could potentially reduce cerebral oxygen consumption as well as ischemia-reperfusion injury resulting in better survival and neurological outcome in a mouse model [19,28].Ketamine was recommended in the hemodynamically unstable patient.However, in rapid sequence induction, ketamine was associated with cardiac arrests and even worse rates of hypotension compared to etomidate, which, despite its potentially beneficial hemodynamic effects, has long been controversial because of concerns about adrenal suppression and was not used in the present work [8,10,29,30] However, the optimal drug combination for postcardiac arrest anesthesia is still unknown.The present study indicates that future studies are needed to detect the influence of postcardiac arrest anesthesia on survival and neurological outcome as well as an optimal substance or combination of substances within the framework of future structured prehospital postresuscitation care.

Limitations
Limitations include the restrictions akin to retrospective studies e.g.underreporting.There is risk of selection bias, as patients who received anesthetic drugs and died in the prehospital setting were not included in the study.The proportion of patients with Out-of-hospitalcardiac arrest as a result of induction of anesthesia in the study cohort was low (Fig. 1).Confounding by indication cannot be excluded as it is likely that unconscious patients were not sedated.Possibly, patients who recover well from cardiac arrest and are then relatively hemodynamically stable are more likely to receive analgesic and hypnotic medications in comparison to their less stable counterparts.There are several unmeasured confounders that can impact the evaluated target parameters of postresuscitation care (e.g.ventilatory settings after intubation, use of positive end-expiratory pressure etc.).Furthermore, they refer to the handover of the patient in hospital and do not allow any statement concerning the time required to correct possible deviations from the recommended parameters during the operation.Due to technical limitations of prehospital monitoring equipment, such as SpO2 or noninvasive blood pressure in centralized or hypothermic patients, flawed measurements Fig. 2 Odds ratios of target parameters of postrescuscitation care in comparison of the groups: postcardiac arrest anesthesia vs. non postcardiac arrest anesthesia.etCO 2 , endtidal CO 2 ; LCL, lower confidence limit; OR, odds ratio; RRsys, systolic blood pressure; SpO 2 , peripheral oxygen saturation; UCL, upper confidence level are possible.It is therefore possible that the proportion of patients who achieved the target parameters was underestimated.The etCO2 may be influenced by things such as aspiration of blood or gastric contents, cardiac output, or severity of lung injury and other reasons and therefore does not always correlate well with the arterial pCO2.
Furthermore, the present study investigated the effects of postcardiac arrest anesthesia on target parameters of hemodynamics, oxygenation and ventilation of postresuscitation care.Therefore, it does not allow any conclusions about the impact of postcardiac arrest anesthesia on patient outcome.However, the positive influence of achieving these target parameters on outcome has been proven in studies that form the basis of current guidelines [4.

Conclusion
Prehospital postcardiac arrest anesthesia is frequent and predominantly executed using hypnotics.While prehospital postcardiac arrest anesthesia was associated with a significant improvement in the achievement of ventilation and oxygenation goals in the prehospital setting, the present study showed no evidence of an increased rate of hemodynamic complications or deviations from hemodynamic target parameters during transfer to hospital.

Meetings
Parts of the present work have been presented as an abstract at the Congress of the German interdisciplinary association for intensive care and emergency medicines (DIVI 2022) 30.11.-02.12.2022,Hamburg, Germany and the German interdisciplinary emergency medicine congress (DINK 2023) 09.03.2023-10.03.2023,Koblenz, Germany.

Table 1
Characteristics of the patients included, the emergency physicians involved and the resuscitation measures performed

Table 2
Characteristics of the conducted postcardiac arrest anesthesia (n = 482)

Table 3
Overview of odds ratios comparing the groups: postcardiac arrest anesthesia vs. no-postarrest anesthesia